Women who have high levels of the inflammatory marker C-reactive protein at the time of breast cancer diagnosis may have worse outcomes, researchers say.

Action Points

Explain that women who have high levels of C-reactive protein (CRP) at the time of breast cancer diagnosis may have worse outcomes.

Note that elevated CRP levels were associated with reduced overall and disease-free survival as well as an increased risk of death, but not with recurrence.

Women who have high levels of C-reactive protein (CRP) at the time of breast cancer diagnosis may have worse outcomes, researchers say.

Those with the greatest concentrations of the inflammatory marker had significantly reduced overall and disease-free survival and a higher risk of death from breast cancer than did those with the lowest concentrations, Kristine Allin, MD, of Copenhagen University Hospital, and colleagues reported in BMC's Breast Cancer Research.

"Measuring CRP levels for breast cancer patients seems to be an easy way to predict the severity of the patient's disease," Allin said in a statement. "This may allow clinicians to alter their treatment tactics and improve cancer survival rates."

Some evidence has suggested that inflammatory pathways play an important role in breast cancer progression in particular.

So to evaluate whether levels of the protein at diagnosis of breast cancer are associated with overall survival, disease-free survival, death from breast cancer, and recurrence, the researchers looked at 2,910 women from the Copenhagen Breast Cancer Study.

They were followed for up to seven years after diagnosis, with a mean of three years. During that time, 383 women died during and 118 had a recurrence.

Allin and colleagues found that elevated CRP levels were indeed associated with reduced overall and disease-free survival as well as an increased risk of death, but not with recurrence.

In adjusted analyses, women in highest CRP tertile had much higher odds of having reduced overall survival than those in the lowest tertile (HR 1.84, 95% CI 1.39 to 2.45, P<0.001).

The same was true of reduced disease-free survival (HR 1.65, 95% CI 1.26 to 2.15, P<0.001).

This group also had a 66% increased risk of death from breast cancer (95% CI 1.15 to 2.41, P=0.005).

With regard to recurrence, incidence was highest among those in the highest tertile of CRP, but it did not increase stepwise with increasing protein levels, the researchers said.

That may have been attributable to a lack of statistical power, since there were only 118 recurrences, they explained.

In further sensitivity analyses, when the cohort was split into octiles, women with the highest CRP levels had 2.5-fold increased risk of reduced survival compared with the lowest octile (95% CI 1.52 to 4.10, P<0.001).

And among those with HER2-positive tumors, the highest octile had far greater risk of reduced overall survival than the lowest (HR 8.63, 95% CI 2.04 to 36.4, P<0.001).

Allin and colleagues said plasma CRP may reflect the aggressiveness of the tumor, as elevated levels were associated with larger tumor size, presence of distant metastases, and lower tumor grade in their study.

It may also express the magnitude and the nature of any inflammation in the breast tumor microenvironment, which could have implications for tumor growth, they wrote.

As well, CRP may say something about the general health of the patient at the time of diagnosis.

The researchers cautioned, however, that they didn't screen for serum amyloid A, which has previously been associated with an even stronger increase in risk of death than CRP.

They also noted that the findings may not be generalizable outside of the Danish population.

Still, they called their findings novel and said CRP levels at breast cancer diagnosis may indeed be predictive of outcomes, regardless of tumor characteristics and lifestyle factors.

The study was supported by the Danish Medical Research Council, the Research Council at Herlev Hospital, Copenhagen University Hospital, and the Chief Physician Johan Boserup and Lise Boserups Fund.

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